As clinicians, our responsibility is to be honest with our patients. To achieve the goal of an honest discourse with this patient, we must inform her that it is uncertain whether she would benefit from carotid endarterectomy (CEA).

Although the landmark clinical trials that compared CEA plus optimal medical therapy (OMT) with OMT alone showed robust benefit for CEA in symptomatic patients with high-grade stenosis, we should acknowledge that studies such as the North American Symptomatic Carotid Endarterectomy Trial (NASCET) used what now would be regarded as “suboptimal” medical therapy. Furthermore, the 70% to 99% cohort of NASCET was published in 1991. It is shocking that clinicians are still making CEA decisions based on data that are 22 years old!

What can we learn from more contemporary stroke prevention studies that have used aggressive medical therapy? A good place to start would be the Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis (SAMMPRIS) study1 Similar to the patient in this scenario, SAMMPRIS included recently symptomatic patients with severe (70%–99%) stenosis. The OMT cocktail included dual antiplatelet therapy, aggressive use of high-potency statins with a target low-density lipoprotein of <70 mg/dL, guideline-derived blood pressure management, and lifestyle modification, including efforts directed toward smoking cessation and regular exercise. The OMT regimen in SAMMPRIS was a spectacular success, so much so that the study was halted by the data monitoring committee, with the conclusion that aggressive medical therapy was superior to intracranial angioplasty with stent placement. The SAMMPRIS OMT cocktail could easily be applied to the patient in question. If it was a spectacular success for recently symptomatic, severe, intracranial stenosis, why wouldn’t it work for recently symptomatic, severe, extracranial disease?

There is suggestive evidence to support the value of aggressive medical therapy for carotid stenosis. First, in an analysis from the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial, patients with carotid stenosis who were treated with high-dose (80 mg) atorvastatin had a 33% reduction in stroke and a 56% reduction in later carotid revascularization compared with placebo.2 Second, dual antiplatelet therapy has been shown to reduce cerebral microembolic signals to a greater degree than aspirin monotherapy. In patients with recently symptomatic carotid stenosis, dual antiplatelet therapy reduced microembolic signals by 40% compared with aspirin alone.3 In this randomized trial of 107 patients, there were 4 strokes and 7 transient ischemic attacks in the aspirin monotherapy group compared with 0 strokes and 4 transient ischemic attacks in the dual antiplatelet therapy group. Finally, in NASCET, the entry systolic blood pressure was 145.2 and 146.2 mm Hg for medical and surgical patients, respectively. By year 2, both groups were at 147.6 mm Hg. This is not concordant with modern guidelines, and current target-driven blood pressure management would likely reduce stroke by at least 20%.

Are there any features of this patient, in particular, that make medical therapy attractive? First, we know that women derive a lower degree of benefit from CEA than men. In the previous pooled analysis by Rothwell et al,4 for symptomatic patients with 50% to 99% stenosis, the number needed to treat with CEA to prevent 1 stroke was 9 for men and 36 for women. Also, it is crucial to recognize that the patient’s transient ischemic attack was 4 weeks ago. Rothwell et al4 have shown that women, in particular, have a narrow window of time in which they can potentially benefit from CEA. Even with “old-fashioned” medical therapy, symptomatic women with 70% to 99% stenosis only showed benefit if CEA was performed when the last symptomatic event was within 2 weeks of randomization. This female patient would have her CEA performed >4 weeks after the last transient ischemic attack, raising serious doubt about whether she would benefit from CEA. Finally, a systematic review found that women tend to experience a higher rate of perioperative stroke/death (odds ratio, 1.31) compared with men, making medical therapy more appealing.

For these reasons, I would argue that intensification of medical therapy and adoption of the SAMMPRIS medical regimen for this patient would be very reasonable. In fact, a Women’s Carotid Artery Stenosis Trial to explicitly test the potential value of aggressive medical therapy versus revascularization for women with severe carotid stenosis would be of great clinical and scientific interest. Hopefully, our female patients with symptomatic carotid stenosis will not need to wait another 22 years to have the merits of contemporary, OMT tested.

Disclosures

Dr Chaturvedi is a consultant to Abbott Vascular, WL Gore, and Thornhill Research.

Footnotes

The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association. This article is Part 2 of a 3-part article. Parts 1 and 3 appear on pages 2955 and 2959, respectively.